This Program Grant brings together individuals from several institutions with the laboratory, clinical, and epidemiological resources and expertise to continue investigations on the natural history and epidemiology of genital herpes simplex virus (HSV) infection. During the course of the initial grant period, the development by our group of a specific, sensitive, reproducible and simple immunodot enzyme assay to measure serum HSV type 1 and HSV type 2 antibodies has allowed the prevalence of genital (and non- genital) herpes to be determined in the U.S. population as a whole (NHANES* ll Project), as well as in several subgroups (college students; lower and middle socioeconomic pregnant women; a Health Maintenance Organization middle class population; STD Clinic patients - heterosexual and homosexual). The prevalence was found to vary greatly according to age, sex, race, and socioeconomic and sexual behavior patterns. In addition, the majority of genital HSV infections were noted to be asymptomatic and to be transmitted subclinically in both males and females. In current proposal, the newly developed serological test will be applied to the NHANES lll probability sample of the U.S. population, which will begin in 1988; this will allow the determination of trends in genital (and non-genital) herpes since the NHANES ll (late 1970's) survey, as well as to obtain correlates of such changes with demographic and other variables. Further detailed focus on the risk factors of acquisition of genital HSV infection will be evaluated in two subgroups: (a) sexually-active heterosexuals and (b) steady couples, in whom one partner is HSV- 2 antibody positive and the other negative. In view of the current practical problems in the management of pregnant women with genital herpes, we will examine the potential usefulness of HSV type antibody testing as a predictor of the shedding of infectious virus at the time of delivery - a possible risk to the neonate. Furthermore, application of the methods, will provide more direct approach to the understanding of reactivation patterns and the natural history of genital herpes in compromised hosts. Studies on natural defense mechanisms to HSV, which could influence the varied virus shedding patterns and clinical expressions of the first infection in the normal host or of reactivated infection in the compromised host, should convey new insights into the complex biological problems associated with HSV infections. Overall then, the proposed projects should provide unique information on the patterns of genital herpes in the late 1980's and early 1990's. The various methods used for risk ascertainment regarding: (a) acquisition of the virus; (b) clinical expression of the infection and (c) risk of viral transmission to others- should offer more rational guidelines in the application of intervention measures. One or more of these possible approaches - vaccines, chemoprophylaxis, or barrier methods - will be studied during the course of this program.